ArticleMolecular cancer research : MCR2008
Transforming growth factor-beta signaling-deficient fibroblasts enhance hepatocyte growth factor signaling in mammary carcinoma cells to promote scattering and invasion.
Article in Molecular cancer research : MCR, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 157 citations in OpenAlex.
- Trial
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- Ursolic Acid's Alluring Journey: One Triterpenoid vs. Cancer Hallmarks.Molecules (Basel, Switzerland) · 2023Review
- Involvement of abnormal dystroglycan expression and matriglycan levels in cancer pathogenesis.Cancer cell international · 2022Review
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- An Update to Hallmarks of Cancer.Cureus · 2022Review
- Theranostic Interpolation of Genomic Instability in Breast Cancer.International journal of molecular sciences · 2022Review
- Proliferation and Apoptosis Pathways and Factors in Oral Squamous Cell Carcinoma.International journal of molecular sciences · 2022Review
- LHPP suppresses colorectal cancer cell migration and invasion in vitro and in vivo by inhibiting Smad3 phosphorylation in the TGF-β pathway.Cell death discovery · 2021Article
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- Research Progress of Bile Acids in Cancer.Frontiers in oncology · 2021Review
- Proliferation Cycle Transcriptomic Signatures are Strongly associated With Gastric Cancer Patient Survival.Frontiers in cell and developmental biology · 2021Article
- Collective cancer cell invasion in contact with fibroblasts through integrin-α5β1/fibronectin interaction in collagen matrix.Cancer science · 2020Article
- Mining TCGA database for genes of prognostic value in gastric cancer microenvironment.Journal of cellular and molecular medicine · 2020Article
- CM082, a novel angiogenesis inhibitor, enhances the antitumor activity of gefitinib on epidermal growth factor receptor mutant non-small cell lung cancer in vitro and in vivo.Thoracic cancer · 2020Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Fibroblasts are major cellular components of the tumor microenvironment, regulating tumor cell behavior in part through secretion of extracellular matrix proteins, growth factors, and angiogenic factors. In previous studies, conditional deletion of the type II transforming growth factor-beta (TGF-beta) receptor in fibroblasts (Tgfbr2FspKO) was shown to promote mammary tumor metastasis in fibroblast-epithelial cell cotransplantation studies in mice, correlating with increased expression of hepatocyte growth factor (HGF). Here, we advance our findings to show that Tgfbr2(FspKO) fibroblasts enhance HGF/c-Met and HGF/Ron signaling to promote scattering and invasion of mammary carcinoma cells. Blockade of c-Met and Ron by small interfering RNA silencing and pharmacologic inhibitors significantly reduced mammary carcinoma cell scattering and invasion caused by Tgfbr2FspKO fibroblasts. Moreover, neutralizing antibodies to c-Met and Ron significantly inhibited HGF-induced cell scattering and invasion, correlating with reduced Stat3 and p42/44MAPK phosphorylation. Investigation of the signal transducer and activator of transcription 3 (Stat3) and mitogen-activated protein kinase (MAPK) signaling pathways by pharmacologic inhibition and small interfering RNA silencing revealed a cooperative interaction between the two pathways to regulate HGF-induced invasion, scattering, and motility of mammary tumor cells. Furthermore, whereas c-Met was found to regulate both the Stat3 and MAPK signaling pathways, Ron was found to regulate Stat3 but not MAPK signaling in mammary carcinoma cells. These studies show a tumor-suppressive role for TGF-beta signaling in fibroblasts, in part by suppressing HGF signaling between mammary fibroblasts and epithelial cells. These studies characterize complex functional roles for HGF and TGF-beta signaling in mediating tumor-stromal interactions during mammary tumor cell scattering and invasion, with important implications in the metastatic process.
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